Week 1 PSL Blood PDF

PSL301H—Blood and Immune System Lecture 3: Acquired Immunity Learning objectives List the four features of acquired immunity Describe how these features are achieved Describe how B cells are activated Describe how antibodies protect us Textbook reading: 8th ed. 768-771, 773 (7th ed. 765-770, 773; 6t...

PSL301H—Blood and Immune System Lecture 3: Acquired Immunity Learning objectives List the four features of acquired immunity Describe how these features are achieved Describe how B cells are activated Describe how antibodies protect us Textbook reading: 8th ed. 768-771, 773 (7th ed. 765-770, 773; 6th ed. 814818, 822; 5th ed. 794-798, 800) Defence against pathogens Innate Immunity rapid, non-specific Acquired Immunity slower, specific Figure from Interactive Physiology Case study : Leon’s case study continued Leon’s doctor suggests he let the head of his student residence know about his infection so that the head can let other students know that they should get the vaccine if they have not already been immunized. 1) What is the purpose of the vaccine? 2) Explain how the body responds to a vaccine. What are the features of acquired immunity? Specificity – activated by and responds to a specific antigen Versatility – ready to confront any antigen at anytime Memory – “remembers” any antigen it has encountered Tolerance – responds to foreign substances but ignores normal tissues Figure from Interactive Physiology Antigens Antibody How are these features achieved? 1. Specificity –responds to a specific antigen Both B and T cells have receptors that recognize specific shapes 2. Versatility – ready to confront any antigen at anytime Different B and T cells have different receptors 3. Memory – “remembers” any antigen it has encountered Some activated B and T cells are long lasting 4. Tolerance – responds to foreign substances but ignores normal tissues B and T cells with receptors that recognize self are deleted or not activated (1) Specificity & (2) versatility of B and T cell receptors B cells T cells Figure from Interactive Physiology B cell receptors bind to extracellular antigens Figure from Interactive Physiology Immunoglobulin-like molecule T cell receptors bind to antigens displayed on the surface of cells (macrophages, tissue cells, etc) T cell receptor Viral antigen Major histocompatability complex Figure from Interactive Physiology T and B cells circulate throughout the body searching for antigen Encounter antigen in secondary lymphoid tissues Figure from Interactive Physiology Clonal selection, expansion and memory Figure 24.11 Primary and Secondary Immune Responses i.e. (3) Memory Figure 24.13 B and T lymphocytes originate in the bone marrow Need to be educated i.e. (4) Tolerance T cells undergo positive and negative selection in the thymus B cells undergo positive and negative selection in the bone marrow Figure from Interactive Physiology Review question When Leon became ill with meningitis, Tom (Leon’s roommate) did not become sick. What is the most likely explanation for this? A. His immune system is hyperactive. B. He has memory NK cells that recognize the bacterium. C. He has memory T and B cells that recognize the bacterium. D. He has a mutation in complement protein 8 (C8) that makes it extra effective at forming the membrane attack complex. Case study : Leon’s case study continued Leon’s doctor suggests he let the head of his student residence know that he has meningitis so that the head can let other students know that they should get the vaccine if they have not already been immunized. 1) What is the purpose of the vaccine? 2) Explain how the body responds to a vaccine. Focus: B cells and Humoral Immunity Antibodies Figure 24.7 Every human has between 107 and 109 different shaped Fabs How are B cells activated? 1. Antigen binds to specific B cell. 2. Antigen is internalized, digested and combined with MHC and then transported to cell surface B cell receptor MHC B cell Antigen Modified figure from Interactive Physiology 2. Specific helper T cell recognizes antigen and MHC becomes activated and secretes cytokines T cell receptor MHC B cell receptor B cell Antigen Helper T cell + cytokines (IL-4, IL-5, IL-6) Modified figure from Interactive Physiology 3. Activated B cell divides. Some daughter cells become plasma cells and secrete antibodies, others become memory B cells cytokines Figure from Martini (2006) Fundamentals of Anatomy and Physiology Summary Figure from Martini (2006) Fundamentals of Anatomy and Physiology How do antibodies protect us? 6 Activates complement Antigen binding site 1 Antigen binds to antibody Complement 5 Triggers mast cell degranulation Antibody Memory cells Plasma cells Secrete antibodies NK cell or eosinophil 4 Activates antibodydependent cellular activity Activates B lymphocytes 2 Acts as opsonins Bacterial toxins 3 Causes antigen clumping and inactivation of bacterial toxins Enhanced phagocytosis Figure ~24.14 Copyright © 2010 Pearson Education, Inc. Classes of antibodies Most common type of circulating antibody Transferred across the placenta from mother to baby First type of antibody to be secreted in response to a new antigen Good at causing antigen clumping and activating complement IgA IgE IgD Crosses epithelial cells. Protects epithelial surfaces and present in breast milk Fights parasites. Eosinophils have receptors for the IgE. Release histamine. Role? Figure from Interactive Physiology Review question The following are steps in the activation of B cells in response to an antigen. Put the steps in the correct order: 1) 2) 3) 4) 5) Some of the B cells differentiate into plasma cells. Plasma cells secrete antibody. T cell secretes cytokines. Antigen is internalized by the B cell. Antigen is presented on MHC molecules on B cells. 6) Antigen binds the B cell receptor. 7) T cell recognizes antigen on B cells. Types of humoral immunity Vaccination with antigen Figure from Interactive Physiology Vaccination with antibodies Coordination of innate and specific immune system: response to extracellular bacteria External environment Skin or mucous membrane lyses ECF coat Bacteria Opsonins present antigens to ingest and disable act as Membrane attack complex activate make Complement proteins activate Mast cells are TH cells Phagocytes Acute phase proteins secrete Chemotaxins Histamine activate increases permeability B lymphocytes become secrete Antibodies Plasma cells act as Plasma proteins Capillary Circulating leukocytes attract Figure 24.16 Monday’s class To be continued Textbook reading: 8th ed. 772-775, 777778) (7th ed. 770-773, 777-778; 6th ed. 818824; 5th ed. 798-804) Case study: Beatrice is a 26-year-old pregnant woman with blood type A-. Her partner is type O+. Questions: 1) Why is this cause for concern? 2) What have Beatrice’s doctors done to alleviate this concern? PSL301H—Blood and Immune System Lecture 2: Pathogens and Innate Immunity Learning outcomes List the overall function of the immune system Describe the main types of pathogens Describe the components of the immune system List and describe the key elements of the innate immune system Be able to predict the effect of stimulating/blocking elements of the innate immune system Textbook reading: 8th ed. 754-767; (7th ed. 754-765; 6th ed. 802-814, 5th ed. 783-793) Overall function of the immune system Destroys pathogens Detects and kills abnormal cells Remove cell debris from body ghr.nlm.nih.gov/.../apoptosismacrophage.jpg Case study: Leon Leon was doing well in first-year university when he developed a cough and diarrhea. He felt very tired and achy and went to bed early. The next morning he had a severe headache and his neck seemed to be stiff. He went immediately to his doctor. He appeared confused and had a temperature of 39.2C. He had small areas of reddish-purple discoloration on his chest, a red throat and enlarged tonsils. 1) What condition might he be suffering from? 2) Given his enlarged tonsils and fever, he likely has an infection, how does the body fight infection? 3) What is the cause of his fever? Types of pathogens Parasitic worms Fungi Protozoa Intracellular and extracellular Bacteria Viruses Figures from Interactive Physiology Viruses Require cells to replicate Figure 24.1 Case study: Leon Leon was doing well in first-year university when he developed a cough and and diarrhea. He felt very tired and achy and went to bed early. The next morning he had a severe headache and his neck seemed to be stiff. He went immediately to his doctor. He appeared confused and had a temperature of 39.2C. He had small areas of reddish-purple discoloration on his chest, a red throat and enlarged tonsils. 1) What condition might he be suffering from? a) Common cold b) Strep throat c) Meningitis d) Influenza Blood cultures revealed that he had Neisseria meningitidis (meningococcus), which causes meningitis FYI symptoms of meningitis Interesting case video of student with meningitis: https://www.youtube.com/watch?v=dYtSWwAndMk Case study: Leon 2) Given his enlarged tonsils and fever, he likely has an infection, how does the body fight infection? Defence against pathogens Innate Immunity rapid, non-specific Acquired Immunity slower, specific Figure from Interactive Physiology Components of the immune system Tonsils are diffuse lymphoid tissue Lymph nodes Spleen Thymus produces T lymphocytes Bone marrow produces most blood cells Encapsulated lymphoid tissues Gut-associated lymphoid tissue (GALT) is a diffuse lymphoid tissue Lymphatic vessels (a) Figure 24.2 Lymphatics Figure from Interactive Physiology 1) Return excess tissue fluid to the blood 2) Transport pathogens/dendritic cells to lymph nodes 3) Transport fat from digestive system to the blood Specialized lymphoid organs Lymph nodes - monitor lymph Figure 24.2 Spleen - monitors blood Figure 24.2 Both contain mature immune cells that interact with pathogens and initiate an immune response Immune cells found in blood, lymph and tissues B lymphocytes T lymphocytes Natural killer (NK) cells tissues tissues Figure 24.2 Defence against pathogens Innate Immunity rapid, non-specific Acquired Immunity slower, specific Figure from Interactive Physiology Elements of the innate immune system 1) Physical barriers 2) Phagocytes -neutrophils – 50-70% WBC -macrophages -dendritic cells 3) Natural killer (NK) cells 4) Antimicrobial proteins 5) Inflammation 6) Fever 1) Physical barriers Figure 24.8 2) Phagocytes diapedesis (extravasation) chemotaxis phagocytosis Figure modified from Molecular Biology of the Cell chemotaxins = e.g. bacterial toxins, products of tissue injury, cytokines Phagocytosis of pathogens Toll-like receptors Pathogen Phagocyte Fc receptors Antibody molecules Polysaccharide capsule Pathogen Antibody receptor Phagocyte Figure 24.9 Antibody is an example of an opsonin Coating substance with an opsonin = opsonization Macrophages and dendritic cells display antigen fragments Lysosome contains enzyme and oxidants Phagosome contains ingested pathogen Antigen-presenting macrophage displays antigen fragments on surface receptors Nucleus Macrophage digests antigen in lysosome Figure 24.10 class II MHC molecule + antigen Review question In rare cases, individuals inherit mutations in a specific toll-like receptors. What process would be impaired in these individuals? A) All phagocytosis in the body B) The ability to defend against extracellular bacteria C) The ability of neutrophils to bind to antibodies D) The ability to defend against bacteria living in cells 3) Natural killer (NK) cells cont’d Kill cells when they are infected with a virus or cancerous Normal cell Virally-infected cell or cancerous cell - MHC class I expression is reduced. Makes the cell susceptible to killing by NK cells Interferons Fig. from: Arthritis Res Ther 2004 6:8 4) Antimicrobial proteins Interferon: a and b – prevent viral replication in cells g – activate macrophages and other immune cells Complement: ~25 plasma proteins Destroy target cell membranes Stimulate inflammation Attract phagocytes Enhance phagocytosis Complement C3 Figure modified from Interactive Physiology Membrane attack complex Complement: Details FYI CLASSICAL PATHWAY Antigen-Antibody (IgG or IgM) Complex C1 Activated C1 C4 + C2 Classical Pathway C3 convertase C4b2a Mannose binding lectins bind mannose on pathogen C3 C4b2a3b C3b C5 LECTIN PATHWAY C3 C5b C6 C7 C8 C9 C3bBb C3b Factor B Microbial Surfaces Membrane Attack Complex C3bBb3b Alternative Pathway C3 convertase Factor D (cleaves Factor B) ALTERNATIVE PATHWAY C5-9 Leon additional information Leon’s doctor learns that he had meningitis in high school and also that 3 of his 5 siblings have also had meningitis. She suspects that he may have a defect in his complement system and orders a CH50 complement test and a genetic test. The tests reveal that Leon and his siblings have a mutation in C8. What process is impaired in Leon and affected his siblings? A) Activation of C1 protein B) Ability to form a membrane attack complex C) Ability to stimulate inflammation D) Ability of his complement proteins to act as an opsonin 5) Inflammation Localized tissue response to injury producing Swelling, redness, heat and pain Roles – Slowing the spread of pathogens – Mobilization of local, regional, and systemic defenses – Sets the stage for repair Figure from Interactive Physiology Inflammatory response Antibody, complement, kinins, clotting factors move into interstitial tissue Figure from Martini (2006) Fundamentals of Anatomy and Physiology Kinin cascade leads to formation of bradykinin – vasodilator and stimulates pain receptors 6) Fever What is the cause of Leon’s fever? Body temperature > 37.2 C Cause: Pyrogens change the thermoregulatory set point in the hypothalamus Roles: Speeds up metabolic activity of host Inhibits some pathogens Pyrogens: e.g. bacterial components, interleukin-1 released from activated macrophages Review question What is needed on/in an infected body cell to cause a natural killer cell to attack it? a) b) c) d) The activation receptor A reduction in MHC class I molecules A receptor for MHC class I molecules The membrane attack complex Friday’s Class Textbook reading: 8th ed. 768-771, 773 (7th ed. 765-770, 773; 6th ed. 814-818, 822; 5th ed. 794-798, 800) Case study : Leon’s case study continued Leon’s doctor suggests he let the head of his student residence know that he has meningitis so that the head can let other students know that they should get the vaccine if they have not already been immunized. 1) What is the purpose of the vaccine? 2) Explain how the body responds to a vaccine. PSL301H—Blood and Immune System Lecture 1: Intro and Red blood cells Learning objectives List the functions of blood Outline the constituents of blood and their functions Understand the process of hematopoiesis Describe the removal of old red blood cells Describe the symptoms of anemia and its possible causes Define polycythemia and state its causes Given a clinical description, be able to accurately predict its possible cause and explain physiological basis of symptoms Textbook reading: Human Physiology: An Integrated Approach. D.U. Silverthorn (2019) Pearson 8th ed. pages 510-522 (7th ed. 512-523; 6th ed. 545-557; 5th ed. 547-557) Functions of blood Transports gases, nutrients, hormones and metabolic wastes Regulates composition of interstitial fluid (e.g. pH, ions, water, etc) Restricts fluid loss at injury sites via blood clotting Defends against toxins and pathogens Regulates body temperature by absorbing and redistributing heat 5 L blood in 70 kg male 4 L blood in 58 kg female Case Study: Erica Fine, a first-year undergraduate student, visited her doctor, complaining of fatigue, irritability, and lightheadedness. Ten years ago, she had been diagnosed with ulcerative colitis. Over the past few months she had omitted animal products from her diet and had eaten only apple sauce for breakfast. 1) List the possible causes of her condition. 2) What tests would you run to make a diagnosis? 3) How would you treat her? The constituents of blood Figure from Martini (2006) Fundamentals of Anatomy and Physiology Hematocrit = % of total blood volume occupied by packed (centrifuged) red blood cells (normal hematocrit = 37-54%) ~Figure 16.1 Plasma 60% 92% 35% 4% Figure 16.1 Most plasma proteins are made by the liver Functions of plasma proteins General: - generate colloid osmotic pressure - buffer pH Specific: Albumins colloid osmotic pressure; carriers Globulins  and b - clotting factors, enzymes, carriers g - antibodies Fibrinogen cleaved to form fibrin in blood clotting ~ Table 16.1 Formed elements 20-40% erythrocytes 99.9% differential white count 2-8% phagocytes leukocytes 0.1% 50-70% thrombocytes 1-4% granulocytes ~54%) high blood viscosity Causes Primary: Abnormal erythrocyte precursors Secondary: Low oxygen delivery to tissues Case study: Leon Leon was doing well in first-year university when he developed a cough and diarrhea. He felt very tired and achy and went to bed early. The next morning he had a severe headache and his neck seemed to be stiff. He went immediately to his doctor. He appeared confused and had a temperature of 39.2C. He had small areas of reddish-purple discoloration on his chest, a red throat and enlarged tonsils. 1) What condition might he be suffering from? 2) Given his enlarged tonsils and fever, he likely has an infection, how does the body fight infection? 3) What is the cause of his fever? Wednesday’s class Immune System--Textbook Reading: 8th ed. 754-767; (7th ed. 754-765; 6th ed. 802-814, 5th ed. 783-793)